Efficacy and Safety of Mycophenolate Mofetil in Refractory IgA Nephropathy

Efficacy and Safety of Mycophenolate Mofetil in Patients With Refractory IgA Nephropathy in Bangladesh: A Phase II Randomized Controlled Trial

This study is testing whether a medicine called mycophenolate mofetil (MMF) works better than the usual treatment for people whose kidney disease, called IgA nephropathy, has not improved with standard care.

IgA nephropathy is a kidney disease that can cause protein to leak into the urine and, over time, can damage the kidneys. Some people with this disease do not get better even after standard treatment. Doctors call this "refractory" disease. Right now, there is no proven best treatment for these patients in Bangladesh.

This study will include 116 adults with kidney disease that has been confirmed by a kidney tissue sample and has not improved with standard treatment. Participants will be split into two equal groups by chance, like a coin flip. One group will take MMF by mouth for 6 months, along with the usual supportive care. The other group will take a steroid medicine called prednisolone, along with the usual supportive care. Both groups will also continue treatments like blood pressure medicines that are already part of standard care for this condition.

Researchers want to find out how many people in each group get better, meaning their urine protein drops to a low level and their kidney function stays stable. They will also look at changes in kidney function and any side effects from the medicines.

The study will take place at the National Institute of Kidney Diseases and Urology Hospital in Dhaka, Bangladesh, over about one year. Each participant will be followed for 6 months, with check-up visits and blood and urine tests at the start, at 3 months, and at 6 months.

Study Overview

• Status: Not yet recruiting
• Conditions: IgA Nephropathy
• Intervention / Treatment: Drug: Mycophenolate Mofetil (MMF); Drug: Prednisolon

Detailed Description

IgA nephropathy is one of the most common forms of primary glomerulonephritis worldwide, with disease burden concentrated in Asia. In Bangladesh, epidemiological data remain limited, though hospital-based biopsy series suggest it accounts for roughly 5-10% of biopsy-proven primary glomerular disease. A subset of patients fail to achieve adequate reduction in proteinuria despite optimized renin-angiotensin-system blockade and a course of corticosteroid therapy; this refractory phenotype carries an elevated long-term risk of progression to end-stage kidney disease and currently lacks a clearly defined, evidence-based treatment pathway.

Mycophenolate mofetil (MMF), a selective and reversible inhibitor of inosine monophosphate dehydrogenase, suppresses T- and B-lymphocyte proliferation and has shown biological plausibility for reducing pathogenic galactose-deficient IgA1 immune complex formation in IgA nephropathy. However, clinical trial results to date have been markedly heterogeneous by population: several Chinese cohort studies report meaningful reductions in proteinuria and renal protection, while Western multicentre randomized trials have largely shown neutral or inconclusive results. This geographic divergence has shaped conditional, population-specific guidance in current KDIGO recommendations. No randomized trial has yet evaluated MMF in a South Asian population, where genetic background, immune response profiles, and healthcare delivery context differ from both previously studied East Asian and Western cohorts.

This trial is designed to generate the first prospective, randomized evidence on MMF for refractory IgA nephropathy in a Bangladeshi population, using an active comparator (prednisolone) rather than placebo, reflecting that corticosteroid-based therapy remains the existing standard of care in this setting. MMF was selected as the intervention of interest because it is already available, relatively affordable, and familiar to local nephrologists through established use in transplant medicine, making it a pragmatic candidate for repurposing should efficacy be demonstrated locally - in contrast to newer agents (e.g., targeted-release budesonide, complement inhibitors) that remain largely inaccessible in this setting due to cost and regulatory constraints.

Randomization will use a block design (block size of 6) generated by a computer-based program to maintain balanced allocation across the two arms throughout the enrollment period. As this is an open-label trial with no blinding, outcome assessments rely on objective laboratory measures (24-hour urinary protein, serum creatinine, eGFR by the CKD-EPI equation) rather than subjective clinician-rated endpoints, to limit the impact of unblinding on result interpretation.

Statistical analyses will be performed on an intention-to-treat basis, with a per-protocol analysis conducted as a supplementary sensitivity analysis. Binary outcomes will be modeled using generalized linear mixed-effects models with a logit link, adjusting for baseline proteinuria, baseline eGFR, age, and sex, with treatment effects expressed as adjusted odds ratios and model-based marginal risk differences. Continuous outcomes will be analyzed using linear mixed-effects models with random intercepts for participants to account for within-subject correlation across repeated measures. The composite renal outcome will be analyzed using Kaplan-Meier estimation with Cox proportional hazards regression. Missing data will be handled under a missing-at-random assumption using maximum likelihood estimation within the mixed models, supplemented by multiple imputation and complete-case sensitivity analyses.

Independent oversight will be provided by a Data and Safety Monitoring Board comprising a nephrologist, medicine specialist, epidemiologist, and statistician not otherwise involved in the trial, reviewing interim safety and efficacy data at three-monthly intervals.

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mohammad Naheed Hasan; Phone Number: +8801776199864; Email: hasannaheed57@gmail.com
• Study Contact Backup: Name: A.T.M. Sulaiman Kabir; Email: kabirdr24@gmail.com

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1000
    • Dhaka Medical College, Dhaka
    • Contact: Mohammad Afzalur Rashid; Email: afzaluhl@gmail.com
  • Dhaka, Bangladesh, 1207
    • National Institute of Kidney Diseases and Urology
    • Contact: Shah Newaz Dewan; Email: dewanshahnewaz@gmail.com
  • Dhaka, Bangladesh, 1207
    • Shaheed Suhrawardi Medical College Hospital
    • Contact: Mohammad Naheed Hasan; Phone Number: +8801776199864; Email: hasannaheed57@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years Biopsy-proven refractory IgA nephropathy, defined as persistent proteinuria >1.0 g/day despite completion of optimized supportive therapy according to KDIGO recommendations, including corticosteroid and/or immunosuppressive therapy and ACE inhibitor and/or angiotensin receptor blocker therapy (unless contraindicated) for a minimum of six months eGFR ≥30 mL/min/1.73 m² at enrollment

Exclusion Criteria:

• Complete or partial remission of IgA nephropathy at enrollment Secondary IgA nephropathy associated with systemic diseases Diabetes mellitus with diabetic kidney disease or any other known non-IgA cause of proteinuria End-stage renal disease requiring dialysis or previous kidney transplantation eGFR <30 mL/min/1.73 m² at enrollment Active infection requiring systemic antimicrobial therapy Significant hepatic impairment (ALT or AST >3 times the upper limit of normal) Pregnancy, planned pregnancy, or breastfeeding Known hypersensitivity or contraindication to MMF

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMF + Standard Care; Participants will receive mycophenolate mofetil (MMF) 1.5 g/day orally in divided doses for 6 months, in addition to standard supportive care (maximally tolerated ACE inhibitor/ARB therapy, blood pressure control per guideline targets, lifestyle modification, and additional therapies such as SGLT2 inhibitors or statins when clinically indicated). Dose adjustment is permitted at the treating physician's discretion in the event of adverse effects.	Drug: Mycophenolate Mofetil (MMF); dministered orally at a total daily dose of 1.5 g in divided doses for a duration of 6 months. Dose adjustment permitted at the discretion of the treating physician in the event of adverse effects.
Active Comparator: Prednisolone + Standard Care; Participants will receive oral prednisolone 0.8 mg/kg/day, followed by a tapering regimen after the study period according to clinical response and tolerability, in addition to the same standard supportive care described for Arm 1.	Drug: Prednisolon; Administered orally at 0.8 mg/kg/day, followed by a tapering regimen after the study period according to clinical response and tolerability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving complete remission	Complete remission defined as 24-hour urinary protein excretion <0.5 g/day combined with stable renal function (eGFR change within 10% of baseline and no requirement for renal replacement therapy)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving partial remission	Defined as ≥50% reduction in 24-hour urinary protein excretion from baseline, with a final value <1.0 g/day	6 months
Change in 24-hour urinary protein excretion	Absolute change calculated as 6-month value minus baseline value, measured via 24-hour urine collection	6 months
Change in serum creatinine	Difference between follow-up and baseline serum creatinine, measured by standardized laboratory methods	6 months
Change in estimated glomerular filtration rate (eGFR)	Calculated using the CKD-EPI equation; difference between baseline and 6-month values	6 months
Proportion of participants achieving proteinuria <1.0 g/day	Assessed via 24-hour urinary protein excretion at 6 months	6 months
Proportion of participants with ≥30% decline in eGFR	Percentage decline calculated from baseline to 6 months	6 months
Composite renal outcome	First occurrence of any of: ≥30% decline in eGFR from baseline, doubling of serum creatinine, or initiation of renal replacement therapy	6 months
Proportion of patients reporting treatment-related adverse events	Documented from time of informed consent through the last per-protocol visit	6 months
Proportion of patients reporting serious adverse events (SAEs)	As defined by death, life-threatening event, persistent disability, prolonged hospitalization, or important medical event, per protocol definitions	6 months

Collaborators and Investigators

• Sponsor: Shaheed Suhrawardy Medical College and Hospital
• Collaborators: National Institute of Kidney Diseases and Urology Hospital
• Investigators: Principal Investigator: Mohammad Naheed Hasan, Shaheed Suhrawardy Medical College

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: August 20, 2026
• First Submitted That Met QC Criteria: August 20, 2026
• First Posted (Actual): August 25, 2026

Study Record Updates

• Last Update Posted (Actual): August 25, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Bangladesh; Immunosuppressive therapy; IgA nephropathy; Mycophenolate mofetil; Refractory proteinuria
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Urination Disorders; Urological Manifestations; Glomerulonephritis; Nephritis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Glomerulonephritis, IGA; Proteinuria; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Caproates; Mycophenolic Acid
• Other Study ID Numbers: 59.15.0000.138.001.16.0002.25.

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: No plan currently exists to share individual participant data outside the study team. This may be reconsidered following study completion

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No